ArticleScientific reports2019
Macrophages promote a profibrotic phenotype in orbital fibroblasts through increased hyaluronic acid production and cell contractility.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Dipeptidyl peptidase-4 inhibitors suppress myofibroblastic differentiation and hyaluronan synthesis in Graves' orbitopathy fibroblasts.Frontiers in endocrinology · 2026Article
- Macrophage plasticity in thyroid eye disease: dual effects of inflammation and fibrosis.Frontiers in immunology · 2026Review
- Maraviroc attenuates orbital remodeling, inflammation, and lipid dysregulation in a murine model of thyroid eye disease associated with Graves' disease.Frontiers in endocrinology · 2026Article
- The therapeutic revolution in thyroid eye disease: from orbital radiotherapy to teprotumumab and AI.Frontiers in medicine · 2026Review
- Integrative transcriptomic profiling and machine learning reveal hypoxia-associated molecular signatures for precision diagnosis in thyroid eye disease.Human genomics · 2025Article
- M2-like macrophages derived from THP-1 cells promote myofibroblast differentiation of synovial fibroblasts in association with the TGF-β1/SMAD2/3 signaling pathway.Scientific reports · 2025Article
- Three-Dimensional Culture of Orbital Fibroblasts From Thyroid Eye Disease Induce In Vivo-Like Tissue Remodeling and Fibrosis.Investigative ophthalmology & visual science · 2025Article
- Intestinal E. coli-produced yersiniabactin promotes profibrotic macrophages in Crohn's disease.Cell host & microbe · 2025Article
- Network pharmacology and experiments verify the effect of triptolide on extraocular muscle fibrosis.PloS one · 2025Article
- Characteristics of Hyaluronan Metabolism During Myofibroblast Differentiation in Orbital Fibroblasts.Investigative ophthalmology & visual science · 2024Article
- Tapinarof, an Aryl Hydrocarbon Receptor Ligand, Mitigates Fibroblast Activation in Thyroid Eye Disease: Implications for Novel Therapy.Investigative ophthalmology & visual science · 2024Article
- A Comprehensive Review of Thyroid Eye Disease Pathogenesis: From Immune Dysregulations to Novel Diagnostic and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Thyroid-associated ophthalmopathy and ferroptosis: a review of pathological mechanisms and therapeutic strategies.Frontiers in immunology · 2024Review
- Human dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis.Rheumatology (Oxford, England) · 2023Article
- Ogerin mediated inhibition of TGF-β(1) induced myofibroblast differentiation is potentiated by acidic pH.PloS one · 2022Article
- Leptin receptor is a key gene involved in the immunopathogenesis of thyroid-associated ophthalmopathy.Journal of cellular and molecular medicine · 2021Article
- MicroRNA-146a downregulates the production of hyaluronic acid and collagen I in Graves' ophthalmopathy orbital fibroblasts.Experimental and therapeutic medicine · 2020Article
- Fibrosis in dysthyroid eye disease.Eye (London, England) · 2020Article
- Thinking inside the box: Current insights into targeting orbital tissue remodeling and inflammation in thyroid eye disease.Survey of ophthalmologyReview
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Graves' orbitopathy (GO) is an autoimmune inflammatory disease affecting the orbit. Orbital fibroblasts are a key component in GO pathogenesis, which includes inflammation, adipogenesis, hyaluronic acid (HA) secretion, and fibrosis. Macrophages are thought to participate in the immunological stage of GO, but whether they can directly affect the fibroblasts phenotype and modulate disease progression is unknown. We previously showed that GO adipogenic and fibrotic phenotypes could be modelled in a pseudo-physiological 3D environment in vitro. Here, we introduced macrophages in this 3D culture model to investigate role for macrophages in modulating adipogenesis, HA production, and contractility in orbital fibroblasts. Macrophages had a minimal effect on lipid droplet formation in fibroblasts, but significantly increased HA production and cell contractility, suggesting that they may promote the fibrotic phenotype. This effect was found to be mediated at least in part through phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) activation and linked to an increase in actin polymerization and protrusive activity in fibroblasts. Overall our work shows for the first time a direct role for macrophages in modulating the fibroblasts' phenotype in GO, supporting a role for macrophages in the progression of the fibrotic phenotype through induction of HA production and stimulation of the contractile phenotype in orbital fibroblasts.
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Registered trials
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